We found substantial agreement among a large, interdisciplinary cohort of international experts regarding evidence supporting recommendations, and the remaining literature gaps in the assessment, prevention, and treatment of Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) in critically ill adults. Highlighting this evidence and the research needs will improve Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep (disruption) management and provide the foundation for improved outcomes and science in this vulnerable population.

Schizophrenia is a common disorder characterized by psychotic symptoms; diagnostic criteria have been established. Family, twin and adoption studies suggest that both genetic and environmental factors influence susceptibility (heritability is approximately 71%; ref. 2), however, little is known about the aetiology of schizophrenia. Clinical and family studies suggest aetiological heterogeneity. Previously, we reported that regions on chromosomes 22, 3 and 8 may be associated with susceptibility to schizophrenia, and collaborations provided some support for regions on chromosomes 8 and 22 (refs 9-13). We present here a genome-wide scan for schizophrenia susceptibility loci (SSL) using 452 microsatellite markers on 54 multiplex pedigrees. Non-parametric linkage (NPL) analysis provided significant evidence for an SSL on chromosome 13q32 (NPL score=4.18; P=0.00002), and suggestive evidence for another SSL on chromosome 8p21-22 (NPL=3.64; P=0.0001). Parametric linkage analysis provided additional support for these SSL. Linkage evidence at chromosome 8 is weaker than that at chromosome 13, so it is more probable that chromosome 8 may be a false positive linkage. Additional putative SSL were noted on chromosomes 14q13 (NPL=2.57; P=0.005), 7q11 (NPL=2.50, P=0.007) and 22q11 (NPL=2.42, P=0.009). Verification of suggestive SSL on chromosomes 13q and 8p was attempted in a follow-up sample of 51 multiplex pedigrees. This analysis confirmed the SSL in 13q14-q33 (NPL=2.36, P=0.007) and supported the SSL in 8p22-p21 (NPL=1.95, P=0.023).

Objective To determine if a quality improvement (QI) intervention improves sleep and delirium/cognition. Design Observational, pre-post design. Setting A tertiary academic hospital in the US. Patients 300 medical ICU (MICU) patients. Interventions This MICU-wide project involved a “usual care” baseline stage, followed by a QI stage incorporating multi-faceted sleep-promoting interventions implemented with the aid of daily reminder checklists for ICU staff. Measurements and Main Results Primary ICU outcomes were perceived sleep quality and noise ratings (measured on a 0-100 scale using the valid and reliable Richards-Campbell Sleep Questionnaire [RCSQ]) and delirium/coma-free days. Secondary outcomes included ICU and hospital length of stay and mortality. Post-ICU measures of cognition and perceived sleep quality were evaluated in an ICU patient subset. During the baseline and sleep QI stages there were 122 and 178 patients, respectively, with >1 night in the ICU, accounting for 634 and 826 patient-days. Within the groups, 78 (63.9%) and 83 (46.6%) patients received mechanical ventilation. Over the 826 patient-day QI period, checklist item completion rates ranged from 86-94%. In multivariable regression analysis of the QI vs. baseline stages, improvements in overall RCSQ sleep quality ratings did not reach statistical significance, but there were significant improvements in daily noise ratings (mean ± standard deviation: 65.9 ± 26.6 vs. 60.5 ± 26.3, P=0.001), incidence of delirium/coma (odds ratio: 0.46; 95% confidence interval, 0.23-0.89; P=0.02), and daily delirium/coma-free status (odds ratio: 1.64; 95% confidence interval, 1.04-2.58; P=0.03). Improvements in secondary ICU outcomes and post-ICU outcomes did not reach statistical significance. Conclusions An ICU-wide QI intervention to improve sleep and delirium is feasible and associated with significant improvements in perceived nighttime noise, incidence of delirium/coma, and daily delirium/coma-free status. Improvement in perceived sleep quality did not reach statistical significance.

Background Prevention and treatment of delirium is critical due to its common occurrence and associated poor outcomes. Objectives To evaluate antipsychotic medications for preventing and treating delirium. Design Systematic review and meta-analysis. Setting PubMed, EMBASE, and CINAHL and ClinicalTrials.gov databases were searched from January 1, 1988 and November 26, 2013. Participants Adult surgical or medical inpatients. Intervention Antipsychotic administration for delirium prevention or treatment in randomized controlled trials or cohort studies. Measurements Two authors independently reviewed all citations, extracted relevant data and assessed studies for potential bias. Heterogeneity was considered as chi-square p<0.1 or and I2 >50%. Using a random effects model (I2 > 50%) or a fixed effects model (I2 < 50%) we calculated odds ratios (OR) for dichotomous outcomes (delirium incidence and mortality), and mean/standardized mean difference for continuous outcomes (delirium duration, severity, hospital/ICU length of stay (LOS)). Sensitivity analyses included 1) postoperative prevention studies only, 2) exclusion of studies with high risk-of-bias, and 3) typical versus atypical antipsychotics. Results Screening of 10,877 eligible records identified 19 studies. In seven studies comparing antipsychotics to placebo or no treatment for delirium prevention in postoperative patients, there was no significant effect on delirium incidence (OR 0.56; 95% CI 0.23, 1.34; I2 = 93%). Using data reported from all 19 studies, antipsychotic use was not associated with change in delirium duration, severity, hospital or ICU LOS, with high heterogeneity among studies. No association with mortality was detected (OR 0.90; 95% CI 0.62, 1.29; I2 = 0%). Conclusion Antipsychotics for prevention or treatment of delirium is not supported by current evidence. Additional methodologically rigorous studies using standardized outcome measures are needed.